-
Biomaterials Science Feb 2023Polyamidoamines (PAMAMs) are a class of dendrimer with monodispersity and controlled topology, which can deliver biologically active macromolecules (, genes and... (Review)
Review
Polyamidoamines (PAMAMs) are a class of dendrimer with monodispersity and controlled topology, which can deliver biologically active macromolecules (, genes and proteins) to specific regions with high efficiency and minimum side effects. In detail, PAMAMs can be functionalized easily by core modification or surface amendment to encapsulate a wide range of biomacromolecules. Besides, self-assembled, cross-linked and hybrid PAMAMs with customized therapeutic purposes are developed as delivery vehicles, which makes PAMAMs promising for biomacromolecule therapy. In this review, we comprehensively summarize the application of PAMAMs in biomacromolecule delivery from the synthesis of functionalized PAMAM carriers to the development of PAMAM-based drug delivery systems. The underlying strategies for PAMAM functionalization and assembly are first systematically discussed, and then the current applications of PAMAMs for biomacromolecule delivery are reviewed. Finally, a brief perspective on the further applications of PAMAMs concludes, aiming to provide insights into developing PAMAM-based biomacromolecule delivery systems.
Topics: Dendrimers; Drug Delivery Systems; Drug Carriers
PubMed: 36692071
DOI: 10.1039/d2bm01677j -
Molecules (Basel, Switzerland) Sep 2020Biomedicine represents one of the main study areas for dendrimers, which have proven to be valuable both in diagnostics and therapy, due to their capacity for improving... (Review)
Review
Biomedicine represents one of the main study areas for dendrimers, which have proven to be valuable both in diagnostics and therapy, due to their capacity for improving solubility, absorption, bioavailability and targeted distribution. Molecular cytotoxicity constitutes a limiting characteristic, especially for cationic and higher-generation dendrimers. Antineoplastic research of dendrimers has been widely developed, and several types of poly(amidoamine) and poly(propylene imine) dendrimer complexes with doxorubicin, paclitaxel, imatinib, sunitinib, cisplatin, melphalan and methotrexate have shown an improvement in comparison with the drug molecule alone. The anti-inflammatory therapy focused on dendrimer complexes of ibuprofen, indomethacin, piroxicam, ketoprofen and diflunisal. In the context of the development of antibiotic-resistant bacterial strains, dendrimer complexes of fluoroquinolones, macrolides, beta-lactamines and aminoglycosides have shown promising effects. Regarding antiviral therapy, studies have been performed to develop dendrimer conjugates with tenofovir, maraviroc, zidovudine, oseltamivir and acyclovir, among others. Furthermore, cardiovascular therapy has strongly addressed dendrimers. Employed in imaging diagnostics, dendrimers reduce the dosage required to obtain images, thus improving the efficiency of radioisotopes. Dendrimers are macromolecular structures with multiple advantages that can suffer modifications depending on the chemical nature of the drug that has to be transported. The results obtained so far encourage the pursuit of new studies.
Topics: Animals; Anti-Inflammatory Agents; Biomedical Technology; Cell Death; Dendrimers; Diagnostic Imaging; Humans; Toxicity Tests
PubMed: 32882920
DOI: 10.3390/molecules25173982 -
Molecules (Basel, Switzerland) Sep 2020Nanostructured hyperbranched macromolecules have been extensively studied at the chemical, physical and morphological levels. The cellular structural and functional... (Review)
Review
Nanostructured hyperbranched macromolecules have been extensively studied at the chemical, physical and morphological levels. The cellular structural and functional complexity of neural cells and their cross-talk have made it rather difficult to evaluate dendrimer effects in a mixed population of glial cells and neurons. Thus, we are at a relatively early stage of bench-to-bedside translation, and this is due mainly to the lack of data valuable for clinical investigations. It is only recently that techniques have become available that allow for analyses of biological processes inside the living cells, at the nanoscale, in real time. This review summarizes the essential properties of neural cells and dendrimers, and provides a cross-section of biological, pre-clinical and early clinical studies, where dendrimers were used as nanocarriers. It also highlights some examples of biological studies employing dendritic polyglycerol sulfates and their effects on glia and neurons. It is the aim of this review to encourage young scientists to advance mechanistic and technological approaches in dendrimer research so that these extremely versatile and attractive nanostructures gain even greater recognition in translational medicine.
Topics: Animals; Anti-Inflammatory Agents; Brain; Brain Neoplasms; Dendrimers; Humans; Neurons
PubMed: 33007959
DOI: 10.3390/molecules25194489 -
Molecules (Basel, Switzerland) Sep 2018Polyamidoamine (PAMAM) dendrimers are one of the smallest and most precise nanomolecules available today, which have promising applications for the treatment of brain... (Review)
Review
Polyamidoamine (PAMAM) dendrimers are one of the smallest and most precise nanomolecules available today, which have promising applications for the treatment of brain diseases. Each aspect of the dendrimer (core, size or generation, size of cavities, and surface functional groups) can be precisely modulated to yield a variety of nanocarriers for delivery of drugs and genes to brain cells in vitro or in vivo. Two of the most important criteria to consider when using PAMAM dendrimers for neuroscience applications is their safety profile and their potential to be prepared in a reproducible manner. Based on these criteria, features of PAMAM dendrimers are described to help the neuroscience researcher to judiciously choose the right type of dendrimer and the appropriate method for loading the drug to form a safe and effective delivery system to the brain.
Topics: Animals; Blood-Brain Barrier; Brain Diseases; Dendrimers; Drug Carriers; Humans; Particle Size; Polyamines
PubMed: 30177605
DOI: 10.3390/molecules23092238 -
Advances in Colloid and Interface... Jul 2018PAMAM dendrimers have been conjectured for a wide range of biomedical applications due to their tuneable physicochemical properties. However, their application has been... (Review)
Review
PAMAM dendrimers have been conjectured for a wide range of biomedical applications due to their tuneable physicochemical properties. However, their application has been hindered by uncertainties in their cytotoxicity, which is influenced by dendrimer generation (i.e. size and surface group density), surface chemistry, and dosage, as well as cell specificity. In this review, biomedical applications of polyamidoamine (PAMAM) dendrimers and some related cytotoxicity studies are first outlined. Alongside these in vitro experiments, lipid membranes such as supported lipid bilayers (SLBs), liposomes, and Langmuir monolayers have been used as cell membrane models to study PAMAM dendrimer-membrane interactions. Related experimental and theoretical studies are summarized, and the physical insights from these studies are discussed to shed light on the fundamental understanding of PAMAM dendrimer-cell membrane interactions. We conclude with a summary of some questions that call for further investigations.
Topics: Animals; Cell Membrane; Cell Survival; Dendrimers; Drug Delivery Systems; Humans
PubMed: 30008347
DOI: 10.1016/j.cis.2018.06.005 -
Biomolecular Concepts Jun 2015Recently, there have been tremendous advances in the development of various nanotechnology-based platforms for diagnosis and therapy. These nanoplatforms, which include... (Review)
Review
Recently, there have been tremendous advances in the development of various nanotechnology-based platforms for diagnosis and therapy. These nanoplatforms, which include liposomes, micelles, polymers, and dendrimers, comprise highly integrated nanoparticles that provide multiple functions, such as targeting, imaging, and therapy. This review focuses on dendrimer-based nanocarriers that have recently been developed for 'theranostics (or theragnosis)', a combination of therapy and diagnostics. We discuss the in vitro and in vivo applications of these nanocarriers in strategies against diseases including cancer. We also explore the use of dendrimers as imaging agents for fluorescence imaging, magnetic resonance imaging, X-ray computed tomography, and nuclear medical imaging.
Topics: Animals; Dendrimers; Humans; Magnetic Resonance Imaging; Neoplasms; Optical Imaging; Theranostic Nanomedicine; Tomography, X-Ray Computed
PubMed: 26136305
DOI: 10.1515/bmc-2015-0012 -
Current Pharmaceutical Design 2017Numerous theoretical studies have been performed to iteratively optimize the physicochemical properties such as dendrimer size and surface constituents in solution, as... (Review)
Review
BACKGROUND
Numerous theoretical studies have been performed to iteratively optimize the physicochemical properties such as dendrimer size and surface constituents in solution, as well as their molecular recognition properties for drugs, lipid membranes, nucleic acids and proteins, etc. Molecular modeling approaches such as docking and molecular dynamic (MD) simulations have supported experimental efforts by providing important insights into the structural properties of dendrimers in solution and possible binding properties of drugs at the atomic level.
METHOD
We review the utilization of molecular modelling tools to obtain insight into the study and design of dendrimers, with particular importance placed on the improvement of binding properties of dendrimers for their use as drug nanocarriers and to increase the water solubility properties and drug delivery.
RESULTS
The modeling studies discussed in this review have provided substantial insight into the physicochemical properties of dendrimers in solution, including solvent pH and counterion distribution, at the atomic level, as well as the elucidation of some of the key interactions in solution of unmodified and modified dendrimers with some drugs of pharmaceutics interest and biological systems such as nucleic acids, proteins and lipid membranes.
CONCLUSION
the described studies illustrate that whether simulations will be run at the all-atom or coarse-grained level, physicochemical conditions such as the type of force field, the treatment of electrostatics effects, counterion distribution, protonation state of dendrimers, and dendrimer concentrations which have been probed to play a crucial role in the structural behavior and binding properties must be prudently incorporated in the simulations.
Topics: Dendrimers; Drug Delivery Systems; Molecular Dynamics Simulation; Molecular Structure; Solubility; Water
PubMed: 28245759
DOI: 10.2174/1381612823666170228142429 -
Journal of Materials Chemistry. B Jun 2021DNA nanomaterials have attracted ever-increasing attention over the past decades due to their incomparable programmability and multifunctionality. In particular, DNA... (Review)
Review
DNA nanomaterials have attracted ever-increasing attention over the past decades due to their incomparable programmability and multifunctionality. In particular, DNA dendrimer nanostructures, as a major research focus, have been applied in the fields of biosensing, therapeutics, and protein engineering, benefiting from their highly branched configuration. With the aid of specific recognition probes and inherent signal amplification, DNA dendrimers can achieve ultrasensitive detection of nucleic acids, proteins, cells, and other substances, such as lipopolysaccharides (LPS), adenosine triphosphate (ATP), and exosomes. By virtue of their void-containing structures and biocompatibility, DNA dendrimers can deliver drugs or functional nucleic acids into target cells in chemotherapy, immunotherapy, and gene therapy. Furthermore, DNA dendrimers are being applied in protein engineering for efficient directed evolution of proteins. This review summarizes the main research progress of DNA dendrimers, concerning their assembly methods and biomedical applications as well as the emerging challenges and perspectives for future research.
Topics: Biomedical Research; DNA; Dendrimers; Humans; Nanostructures; Particle Size
PubMed: 34008692
DOI: 10.1039/d1tb00689d -
Small (Weinheim An Der Bergstrasse,... Nov 2022Dendrimers are polymers with well-defined 3D branched structures that are vastly utilized in various neurotheranostics and biomedical applications, particularly as... (Review)
Review
Dendrimers are polymers with well-defined 3D branched structures that are vastly utilized in various neurotheranostics and biomedical applications, particularly as nanocarrier vectors. Imaging agents can be loaded into dendrimers to improve the accuracy of diagnostic imaging processes. Likewise, combining pharmaceutical agents and anticancer drugs with dendrimers can enhance their solubility, biocompatibility, and efficiency. Practically, by modifying ligands on the surface of dendrimers, effective therapeutic and diagnostic platforms can be constructed and implemented for targeted delivery. Dendrimer-based nanocarriers also show great potential in gene delivery. Since enzymes can degrade genetic materials during their blood circulation, dendrimers exhibit promising packaging and delivery alternatives, particularly for central nervous system (CNS) treatments. The DNA and RNA encapsulated in dendrimers represented by polyamidoamine that are used for targeted brain delivery, via chemical-structural adjustments and appropriate generation, significantly improve the correlation between transfection efficiency and cytotoxicity. This article reports a comprehensive review of dendrimers' structures, synthesis processes, and biological applications. Recent progress in diagnostic imaging processes and therapeutic applications for cancers and other CNS diseases are presented. Potential challenges and future directions in the development of dendrimers, which provide the theoretical basis for their broader applications in healthcare, are also discussed.
Topics: Dendrimers; Drug Carriers; Gene Transfer Techniques; Transfection; Solubility; Drug Delivery Systems
PubMed: 36084240
DOI: 10.1002/smll.202203629 -
Archives of Pharmacal Research Jun 2018Dendrimers offer well-defined nanoarchitectures with spherical shape, high degree of molecular uniformity, and multiple surface functionalities. Such unique structural... (Review)
Review
Dendrimers offer well-defined nanoarchitectures with spherical shape, high degree of molecular uniformity, and multiple surface functionalities. Such unique structural properties of dendrimers have created many applications for drug and gene delivery, nanomedicine, diagnostics, and biomedical engineering. Dendrimers are not only capable of delivering drugs or diagnostic agents to desired sites by encapsulating or conjugating them to the periphery, but also have therapeutic efficacy in their own. When compared to traditional polymers for drug delivery, dendrimers have distinct advantages, such as high drug-loading capacity at the surface terminal for conjugation or interior space for encapsulation, size control with well-defined numbers of peripheries, and multivalency for conjugation to drugs, targeting moieties, molecular sensors, and biopolymers. This review focuses on recent applications of dendrimers for the development of dendrimer-based nanomedicines for cancer, inflammation, and viral infection. Although dendrimer-based nanomedicines still face some challenges including scale-up production and well-characterization, several dendrimer-based drug candidates are expected to enter clinical development phase in the near future.
Topics: Dendrimers; Drug Carriers; Drug Design; Humans; Nanomedicine; Neoplasms; Virus Diseases
PubMed: 29450862
DOI: 10.1007/s12272-018-1008-4